Pharmacology Notes - PDF

Pharmacology introduction:................................................ 1 Indirect Sympathomimetics:................................................9 Parasympathomimetics are classified into:..................... 4 Cholinergic Antagonists: Parasympatholytics.....

Pharmacology introduction:................................................ 1 Indirect Sympathomimetics:................................................9 Parasympathomimetics are classified into:..................... 4 Cholinergic Antagonists: Parasympatholytics............... 10 Sympathomimetic drugs agonist........................................ 6 Sympatholytic (Adrenergic antagonist)......................... 12 Selective D1 agonist:................................................................7 Adrenergic Antagonists....................................................... 12 Alpha & Beta agonist:............................................................7 Alpha Blockers....................................................................... 13 Selective α1 Agonists.............................................................. 8 Beta-Blockers......................................................................... 13 Selective β1 Agonists.............................................................. 8 Alpha & Beta Blockers......................................................... 14 Selective β2 Agonists.............................................................. 8 Selective α1 & Nonselective β Blockers............................. 14 Pharmacology: is the science that deals with the study of drugs, which includes the following branches: Pharmacodynamics Pharmacokinetics Pharmacotherapeutics Toxicology Pharmacodynamics: The effects of drugs on the body, which includes: 1. Mechanism of action (MOA): active part of the cell which forms chemical bonds with drugs. These active parts are: Enzymes Ion channels Cell membrane Receptors DNA synthesis Chemical reaction (neutralization reaction), e.g., Antacid Physical reaction (Adsorption); e.g., charcoal, which is used in toxicity 2. Clinical use (desired effects of drugs) 3. Side effects (undesired effects of drugs) Pharmacokinetics: - is the effect of the body on drugs which includes: Absorption: Transfer of drugs from the site of administration to blood circulation which occurs in the small intestine Factors affecting absorption: A- factors related to the patient: 1. Food: The presence of food ↓ absorption with some exceptions such as antifungal drugs. 2. Health state: either constipation (↑ absorption) or diarrhoea (↓ absorption). B- factors related to drugs: 1. Liquid is more absorbed than solid. 2. Parenteral (injection) is more absorbed than oral 3. Particle size: small size is highly absorbed than large. 1  MED39 1 Pharmacology team 4. Lipid-soluble is more absorbed than water-soluble. Bioavailability: The amount of drug that reaches systemic (blood) circulation. ↑ Bioavailability means ↑ absorption (orally) ↓ Bioavailability means ↓ absorption in such case, we administer the drug other Chapter 1 Distribution: Spread of drugs all over the body to reach different body organs. Factors affecting distribution: ▪ Binding to plasma protein ▪ ↑ Binding to plasma proteins → inactive drugs have a long duration of action (t½). ▪ ↓ Binding to plasma proteins → active drugs Metabolism: The first step of drug elimination in which modification in the chemical structure of drugs. takes place, mainly occurs by liver enzymes. Other sites: GIT, plasma (contains esterase enzyme), kidney, and brain (10%) Aim: a. Conversion of drugs from active (lipid-soluble) to inactive (water-soluble) so it can be excreted. b. Conversion of prodrugs (inactive drugs) to active, e.g., captopril. c. Conversion of drugs from active to active (prolongation of action). d. Conversion of active drugs to toxic metabolites (rare cases). Factors affecting metabolism: 1. Healthy state of the liver (most important). 2. Age. 3. Sex: Drug metabolism occurs in males more than females because androgens [help more synthesis of enzymes]. 4. Drug-drug interaction: 1. Metabolic inducer: Drugs stimulate metabolism which may inactivate other drugs. 2. Metabolic inhibitor: Drugs inhibit metabolism which may cause toxicity of other drugs. Excretion: Removal of drugs outside the body. Site: Kidney (mainly) Other sites: GIT, sweating, lacrimation, salivation, and exhalation Water-soluble drugs (polar) → excretion is more than non-polar drugs. Healthy state of kidney is an important factor in excretion. Pharmacotherapeutics: The art of treatment of disease (Proper choice of drugs with proper dose for each health problem). Toxicology: The science that deals with the study of drug toxicity, which includes: 1. Toxic dose 2. Toxic symptoms 3. Treatment of toxicity 2 Page  MED39 MED39 1 ‫ أمساء علوان‬:‫الدكتورة‬ Pharmacology team Drugs: Any substance of any source which can be used for treatment, diagnosis, and prevention of diseases. Sources of drugs: 1. Synthetic drugs 2. Natural drugs that include: Plant (most important source) as digoxin and atropine Animal as insulin (from horse) Microorganism like fungus (penicillin) Marine (cod liver oil) omega 3 Soil as Zn+2, Mg+2, Ca+2 Route of administration: 1. External: -not reach to blood o produce local effects 2. Internal: -reach blood o orally, parenteral, inhalation, or rectal. Terminology Chapter 1 Agonist: Drug which binds to sympathetic receptor to produce similar effects to the normal neurotransmitter. Antagonist: Drugs bind to sympathetic receptor to block or inhibit the effects of normal neurotransmitter. Tolerance: Loss of drug’s response in which there is a need to increase drug dose to get the same effect (e.g., paracetamol). Tachyphylaxis: Rapid occurrence of tolerance. Dependence: Severe craving to drug in which sudden stop may cause central withdrawal effects which occur as (insomnia, anxiety, and nervousness) e.g., Diazepam. Addiction: Severe craving to drug in which sudden stop may cause peripheral and central withdrawal effect (death may occur) e.g., Morphine, Heroin. Potency: Strength of drugs (concentration of active constituents). Efficacy: Maximum response produced by drug. Onset of action: Time between drug administration and occurrence of effects. Duration of action: Time between occurrence of effects and reoccurrence of the symptoms of disease (effect of drug disappears). Therapeutic index (TI): The degree of drug safety. So, an increase in TI means a safe drug, while a decreased TI means a toxic drug. e.g., In paracetamol, the ED50 = 500mg and TD50=20g, so: TI= (20×1000)÷500=40 In paracetamol, TI= 40 means it’s a safe drug. Drug monitoring: 1. Parameters such as blood glucose, BP. 2. Free of symptoms such as fever, headache. Page 3  MED39 1 Pharmacology team 3. Concentration of drugs in blood. Terminology: 1. Parasympathetic stimulators (Parasympathomimetics). 2. Parasympathetic inhibitors (parasympatholytics). 3. Sympathetic stimulator (sympathomimetic). 4. Sympathetic inhibitor (sympatholytic). Chapter 1 Parasympathomimetics are classified into: Parasympathomimetics (cholinergic agonist): Drugs bind to parasympathetic receptors (N, M) to produce a similar effect to the natural neurotransmitter (ACh). Effects: 1. ↑ Memory and learning. 2. Eye: Miosis ↓ intraocular pressure (IOP) → ↑ drainage of aqueous humour. 3. Cardiac work: ↓ Contraction, ↓ COP, ↓ HR. 4. B.C which will lead to asthma. 5. GIT: ↑ HCl secretion (hyperacidity), ↑ motility (diarrhoea). 6. Nausea and vomiting. 7. Urinary Bladder: Contraction of the wall and relaxation of sphincter → Frequency of urination. 8. Blood vessels: V.D via ↑ NO (indirect effect) which will lead to: A) Hypotension B) Congestion (nasal congestion, redness of eyes). 9. Uterus: ↑ Contraction of wall (abortion). 10. Saliva: ↑ Watery secretion (parasympathetic increases watery secretion and sympathetic decreases it). 11. ↑ Sweating and lacrimation. 12. Contraction of skeletal muscle → by stimulating the nicotinic receptor. Note: All peripheral effects are results from stimulating the muscarinic receptor (M) except in the skeletal muscle which is by stimulating of nicotinic receptors (N). Muscarinic receptors: M1: Parietal cells of the stomach → ↑ HCl secretion. M2: Heart → ↓ HR. M3: All over the body. M4 & M5: In the CNS. Parasympathomimetics are classified into: 1. Direct agonist: The drug binds to the receptor to produce effects directly. It works on the M receptors only. 2. Indirect agonist: The drug increases acetylcholine, then acetylcholine will bind to the receptor and give the effect. It works on both M and N receptors. 4 Page  MED39 MED39 1 ‫ أمساء علوان‬:‫الدكتورة‬ Pharmacology team Direct agonist drugs: Sjogren’s disease Pilocarpine (eye drops): MOA: Stimulates all the M agonists (non-selective). is an autoimmune disease which comes out as dry eye & dry CU: Glaucoma, Sjogren’s disease. mouth the drug is helpful. Bethanechol (oral and parenteral): MOA: M agonist. CU: Glaucoma, postoperative urine retention & paralytic ileus. (Where this drug make contraction of UB which prevents the urine retention and increases the motility of the GIT especially the small intestine) Cevimeline (oral): MOA: Selective M3 agonist. CU: Sjogren’s disease. Indirect agonist drugs: MOA: Ach esterase inhibitors → so it increases the duration of Ach in the body. Chapter 1 Types: Reversible Ach esterase inhibitors: o Block the enzyme for a short duration. Irreversible Ach esterase inhibitors: o Toxic compounds. o The body is under control of the parasympathetic (it takes the upper-hand). Reversible drugs: 1. Physostigmine: o CU: a) Eye drop in glaucoma, b) I.V in acute state such as poisoning. which means that we can use it as antidote for cholinergic antagonist. 2. Neostigmine & Pyridostigmine: CU: Postoperative urine retention and paralytic ileus, Myasthenia gravis. o 3. Donepezil & Rivastigmine: o More selective on central esterase. Notes: They differ in the type of esterase o Used either orally or transdermal patches which they act on: o CU: Dementia, which may be caused by o Donepezil: More selective on Ach degenerative diseases such as esterase in CNS. Alzheimer’s, Parkinson’s disease, or o Rivastigmine: Inhibits both ACh drug-induced as anticholinergic drugs. esterase and butyryl choline esterase. Irreversible compounds: Organophosphate Compounds (Cpd) These are toxic compounds such as: Insecticides: Parathion, Malathion 🐛 War Gases: Sarin, Soman 💣 They lead to: Severe miosis 👁️ Severe sweating with salivation 💦 Bradycardia Convulsion 🤯 Bronchoconstriction 🫁 Decreased B.P (Blood Pressure) Fever 🤒 Diarrhoea and increased urination 🚽 Page 5